Risperidone administration affects homocysteine levels in first episode schizophrenia

Of the many themes that seem to quite consistently surface on this blog looking at the peer-reviewed science in relation to various behavioural/psychiatric labels, the idea that various pharmacological interventions might do quite a bit more than 'what they say on the tin' is a recurring one. Take one case in point (see here)...

Today's offering adds to that theme as the results reported by Ning Fan and colleagues [1] are presented for your reading pleasure and the particular finding that: "Serum Hcy [homocysteine] levels were significantly decreased in schizophrenia patients after risperidone treatment."

OK, a few points need explaining first. Homocysteine is a compound that has also received considerable attention on this blog as per it's involvement in a particular group of intersecting biological cycles with relevance to various diagnostic labels including schizophrenia (see here for example). Alongside other independent pieces of research (see here), the diagnosis of schizophrenia seems to have some important connections to homocysteine although the precise details still need to be properly elucidated.

High levels of homocysteine are generally not thought to be a good thing for quite a few reasons [2] and that goes as much for persons diagnosed with schizophrenia as it does for everyone else. So when elevated plasma levels of homocysteine are recorded, medicine really does need to do something to (a) identify why and (b) try and bring levels back to within a more typical range.

Fan et al reported a few important things in their study of 56 participants "first-episode and drug-naïve inpatients with schizophrenia" compared with a similar number of sex- and age-matched asymptomatic controls. First, plasma homocysteine levels were elevated in those with schizophrenia. Nothing new there. They also reported on some potentially interesting *associations* between elevated homocysteine levels and specific symptoms relevant to schizophrenia: "a significant positive correlation between Hcy levels and PANSS negative sub-score was observed." Finally, they reported that risperidone use seemed to affect homocysteine levels in their clinical group. Interesting.

That last point is rather intriguing. Risperidone is a treatment of choice as per its second generation antipsychotic label and accompanying properties. Despite quite a lot of focus on the side-effects associated with such a medicine (see here for example) it does serve an important purpose for many people. It's mode of action is still under debate but it is generally thought to have some action in relation to effects on one or more neurotransmitter receptors. But... other potential effects have also been noted in the peer-reviewed research literature pertinent to mode of action including some in relation to immune function (see here) and how schizophrenia (some schizophrenia?) *might* have a significant immune component attached to it (see here for example). The Fan results add another potential mode of action to risperidone use and why it may impact on symptom presentation for some diagnosed with schizophrenia and related conditions. I'm not by any means saying that homocysteine is 'causative' of schizophrenia but the Fan results do suggest that quite a few more investigations may be warranted on the connection between schizophrenia, homocysteine and risperidone. Indeed, whether also other homocysteine-lowering compounds may provide some novel intervention options for some diagnosed with schizophrenia (see here) (with no medical or clinical advice given or intended).

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[1] Fan N. et al. Effect of Risperidone on Serum Homocysteine Levels in First-episode, Drug-naïve Patients with Schizophrenia. Neurosci Lett. 2017 Apr 15. pii: S0304-3940(17)30326-9.

[2] Zhang D. et al. Elevated Homocysteine Level and Folate Deficiency Associated with Increased Overall Risk of Carcinogenesis: Meta-Analysis of 83 Case-Control Studies Involving 35,758 Individuals. PLoS ONE. 2015; 10(5): e0123423. 

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Fan N, Tan Y, Yang F, Tian L, Chen S, Li J, Wang Z, & Zhang X (2017). Effect of Risperidone on Serum Homocysteine Levels in First-episode, Drug-naïve Patients with Schizophrenia. Neuroscience letters PMID: 28419824